This invention relates to a method of preventing retinopathy of prematurity in a prematurely born neonate. More particularly this invention relates to a method of preventing retinopathy of prematurity in a prematurely born neonate having a birthweight of less than 1500 grams and a gestational age at birth of less than 32 weeks.
Retinopathy of prematurity is an eye disease which results from abnormal development of the retina, the light-sensitive lining of the eye, in prematurely born babies. The disease generally occurs in both eyes. Not all prematurely born babies develop retinopathy of prematurity, and for many the disease resolves itself without treatment in early stages. However, retinopathy of prematurity remains a common morbidity in very low birth weight infants and it can progress to a serious and potentially blinding eye problem. As the number of highest risk infants who survive increases, so does the number with retinopathy. For those babies in whom retinopathy progresses, treatment is necessary. Cryotherapy and laser treatment have some effect in advanced stages of the disease, saving a degree of vision in a proportion of the eyes that would otherwise have been blinded, but prevention awaits a better understanding of major causative factors and underlying pathophysiology.
The immature state of the retina at the time of premature delivery allows damage to the developing retinal vessels. Retinopathy occurs when abnormal blood vessels and scar tissue form at the edge of the normal retinal blood supply. The two critical areas for predicting which children are most likely to develop retinopathy are birthweight less than 1500 grams and gestational age at birth of less than 32 weeks. Other potential contributors to the disease that are currently under investigation are antenatal steroid use, alkalosis, light, chronic hypoxia, septic shock or septic episodes, and other severe physiological stresses.
If retinopathy of prematurity develops, it usually develops between 34 and 42 weeks of last conceptual age. Regressed retinopathy, whether spontaneous or after treatment, has a high incidence of sequelae such as myopia, strabismus, amblyopia, and other refractive errors. These long term vision problems correlate with abnormal fundoscopic examinations. In addition to visual difficulties, 15% of all infants with retinopathy had an adverse cosmetic outcome, including nystagmus, retrolental membrane, epiphora, corneal opacity, cataract, or episcleral hyperemia. Sometimes infants may develop glaucoma. It was also shown that neonatal retinopathy seems to be a marker for functional disability at age 5.5 years among low birth weight survivors. High rates of functional limitations in multiple domains occur in children who had retinopathy, particularly if they have unfavorable visual acuity.
It has been determined in newborn pigs that the cyclooxygenase pathway contributes to free radical formation after oxidative insults such as asphyxia, and it was demonstrated that non-steroidal anti-inflammatory drugs prevented increase in retinal malondialdehyde and hydroperoxides after asphyxia. It was also shown that indomethacin improved oxygen-induced retinopathy when administered concurrently with the injury phase without affecting the normal growth in the mouse. Nonetheless, epidemiological data suggest that postnatal administration of indomethacin to prematurely born neonates could increase the risk of developing retinopathy of prematurity (ROP).
It is the object of the invention to provide a method of preventing retinopathy of prematurity in a prematurely born infant using a non-steroidal anti-inflammatory agent that does not possess the retinopathy-promoting effects of the non-steroidal anti-inflammatory agent indomethacin.